SAN DIEGO, July 20 /PRNewswire-FirstCall/ -- Orexigen
Therapeutics, Inc. (NASDAQ:OREX)
today announced that all three remaining Phase 3 trials evaluating
Contrave (bupropion SR/naltrexone SR), its investigational drug for
the treatment of obesity, met their co-primary endpoints. The
results from the successfully completed Contrave Obesity Research,
or COR, program of more than 4,500 patients exceed the FDA
categorical efficacy benchmark for clinically significant weight
loss, supporting the Company's plan to file a New Drug Application
(NDA) with the US Food and Drug Administration (FDA) in the first
half of 2010.

Key top-line data from the COR Phase 3 program include the following:
-- 48.0% and 56.3% of patients on Contrave32(1) in COR-I (NB-301) and
COR-II (NB-303) lost at least 5% of their body weight after 56 weeks,
approximately three times the placebo categorical response rates of
16.4% and 17.1%, respectively (ITT, p<0.001).
-- Contrave patients in COR-I and COR-II on Contrave32 had mean weight
loss of 6.1% and 6.4% after 56 weeks, compared to 1.3% and 1.2% on
placebo, respectively (ITT, p<0.001).
-- In the COR-Diabetes (NB-304) trial, 44.5% of patients on Contrave32
lost greater than or equal to 5% of their body weight after 56 weeks,
more than double the 18.9% of patients on placebo (p<0.001). Contrave
patients also showed a 0.6% reduction in HbA1c from baseline, compared
to a 0.1% reduction in placebo. This difference of 0.5% is clinically
and statistically significant (ITT, p<0.001).
-- Key secondary endpoints met across the entire COR Phase 3 program
included significant improvements in cardiovascular and metabolic risk
factors such as waist circumference, visceral fat, HDL cholesterol and
triglycerides.
-- Additional analyses indicate that Contrave patients experienced
reductions in the frequency and strength of food cravings and an
increased ability to control their eating compared to placebo.
-- Contrave was generally well tolerated by patients across the COR Phase
3 program. The COR program data continue to be analyzed and compiled
for submission to relevant scientific conferences, peer-reviewed
journals and regulatory agencies.

"The successful completion of the COR Phase 3 program is a major
milestone for Orexigen, and the results demonstrate the potential
for Contrave to help patients in their battle against obesity,"
said Mike Narachi, President and CEO of Orexigen. "These results
highlight the benefits of Contrave, a novel combination that was
specifically designed to address the behavior and reward pathways
in the brain that impact one's ability to initiate and sustain
weight loss."

All Phase 3 trials in the COR program were 56 week, randomized,
double-blind, placebo-controlled trials. The co-primary endpoints
were the proportion of patients achieving at least 5% weight loss
and percent change in body weight compared to placebo. These
endpoints were analyzed using intent-to-treat (ITT) last
observation carried forward (LOCF) of all randomized patients who
had at least one post-baseline observation while on study drug.
Secondary endpoints included multiple measures of cardiometabolic
risk, food cravings and eating control, as well as HbA1c in the COR
Diabetes trial. Patients were randomized to receive either placebo
or Contrave, BID, with a four week titration period.

Across the entire COR program, seven serious adverse events were
attributed by investigators as possibly related to Contrave
treatment. These include cholecystitis (gallbladder inflammation)
(2), seizure (2), palpitations (1), paresthesia (1) and vertigo
(1). The most frequently observed treatment-emergent adverse events
were nausea, constipation and headache. Nausea was the leading
adverse event resulting in discontinuation; however, for the
majority of patients experiencing nausea, it was mild to moderate,
transient and manageable.

At week 56, mean blood pressure was generally unchanged from
baseline for Contrave patients compared to placebo patients, who
tended to experience a slight decrease (approximately 2 mm Hg) from
baseline. Contrave treatment did not appear to disrupt the normal
circadian pattern of blood pressure. There was a slight increase in
pulse (approximately 1 beat per minute) in Contrave patients
compared to placebo patients, whose pulse was generally unchanged.
There were no meaningful treatment effects on ECGs or laboratory
measures including liver function tests. Treatment with Contrave
was not associated with increases in symptoms of depression or
suicidal ideation.

"The data are remarkably consistent across the COR program,
giving us greater confidence that Contrave has the potential to
help obese patients, even those with diabetes, to initiate and
sustain weight loss and improve their health," said Dr. Ken
Fujioka, Lead Investigator, Director of Nutrition and Metabolic
Research, Scripps Clinic. "These results mark the beginning of an
exciting new era in the treatment of the global obesity epidemic
where drug therapies may play an increasingly important role."

Conference Call

The Company has scheduled a conference call today, July 20, at
8:00 a.m. Eastern Time to discuss further details from these
trials. The live call may be accessed by calling 1-800-561-2813,
(domestic) 617-614-3529 (international); meeting code: 14007929.
The webcast can be accessed live on the investor relations section
of the Company's web site at http://www.orexigen.com/ and will be
archived for 14 days following the call.

About Contrave

Contrave is an investigational medication for the treatment of
obesity believed to have a unique mechanism of action that works at
two levels within the central nervous system: one associated with
controlling the balance of food intake and metabolism and another
involved in controlling food preference, reward and cravings. We
believe that Contrave has the potential to be the first treatment
for obesity to target both of these reward centers in the central
nervous system. Contrave is believed to initiate and sustain
significant weight loss over one year of treatment by reducing
appetite, increasing metabolism and allowing the body to continue
losing weight by offsetting its natural tendency to fight back and
slow down the weight loss process.

Orexigen reported the results of the COR-BMOD (NB-302) trial in
January 2009. This was a 56-week trial designed to assess the
safety, tolerability and efficacy of Contrave32 versus placebo in
793 obese patients combined with an underlying intensive behavior
modification regimen. The trial was conducted at nine U.S. centers.
Patients in that trial who completed one year of treatment on
Contrave lost 11.5% of their body weight, compared to 7.3% on
placebo.

About Orexigen Therapeutics

Orexigen Therapeutics, Inc. is a biopharmaceutical company
focused on the treatment of obesity. The Company's lead
investigational product, Contrave, has completed Phase 3 clinical
trials and is on track for a regulatory submission with the FDA in
the first half of 2010. The Company's second product, Empatic(TM),
is in the later stages of Phase 2 clinical development, with
results expected in the second half of 2009. Each product candidate
is designed to act on a specific group of neurons in the central
nervous system with the goal of achieving appetite suppression and
sustained weight loss, through combination therapeutic approaches.
Further information about the Company can be found at http://www.orexigen.com/.

Forward-Looking Statements

Orexigen cautions you that statements included in this press
release that are not a description of historical facts are
forward-looking statements. Words such as "believes,"
"anticipates," "plans," "expects," "indicates," "will," "intends,"
"potential," "suggests," "assuming," "designed" and similar
expressions are intended to identify forward-looking statements.
These statements are based on the Company's current beliefs and
expectations. These forward-looking statements include statements
regarding the efficacy and safety of Contrave , the potential for,
and timing of, an NDA submission for Contrave, the commercial and
therapeutic potential of Contrave, and the potential to obtain
regulatory approval for, and effectively treat obesity with,
Contrave and Empatic(TM). The inclusion of forward-looking
statements should not be regarded as a representation by Orexigen
that any of its plans will be achieved. Actual results may differ
from those set forth in this release due to the risk and
uncertainties inherent in the Orexigen business, including, without
limitation: additional analyses of data from the Contrave Phase 3
trials and any other clinical trials of Contrave may produce
negative or inconclusive results, or may be inconsistent with
previously announced results or previously conducted clinical
trials; the FDA may not agree with the Company's interpretation of
efficacy and safety results; earlier clinical trials may not be
predictive of future results; Contrave or Empatic may not receive
regulatory approval on a timely basis or at all, and the FDA may
require Orexigen to complete additional clinical, non-clinical or
other requirements prior to the submission or the approval of NDAs
for either product candidate; the potential for adverse safety
findings relating to Contrave or Empatic to delay or prevent
regulatory approval or commercialization, or result in product
liability claims, including serious adverse events that are not
characterized by clinical investigators as possibly related to
Contrave; the third parties on whom Orexigen relies to assist with
the development programs for Contrave or Empatic, including
clinical investigators, contract laboratories, clinical research
organizations and manufacturing organizations, may not successfully
carry out their contractual duties or obligations or meet expected
deadlines, and the quality or accuracy of the data or materials
generated by such third parties may be of insufficient quality to
include in the Company's regulatory submissions; the ability of
Orexigen and its licensors to obtain, maintain and successfully
enforce adequate patent and other intellectual property protection
of its product candidates; Orexigen may be unable to enter a
collaboration or partnership relating to Contrave for promotion to
broader markets on attractive terms or at all; and other risks
described in the Company's filings with the Securities and Exchange
Commission. You are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof,
and Orexigen undertakes no obligation to revise or update this news
release to reflect events or circumstances after the date hereof.
All forward-looking statements are qualified in their entirety by
this cautionary statement. This caution is made under the safe
harbor provisions of Section 21E of the Private Securities
Litigation Reform Act of 1995. Information included herein is based
on the Company's review and evaluation of the clinical data. All
conclusions and determinations contained herein are subject to the
Company's further analysis of the clinical data. The ultimate
determination of the safety and efficacy of Contrave and Empatic
will be made by the FDA and other relevant regulatory
authorities.